Nucleotide sequence of the PSE-4 carbenicillinase gene and correlations with the Staphylococcus aureus PC1 beta-lactamase crystal structure.
The nucleotide sequence of the PSE-4 beta-lactamase gene from Pseudomonas aeruginosa strain Dalgleish has been determined. The structural gene encodes a polypeptide product of 252 amino acids with an estimated molecular mass of 29,246 Da for the mature form of the protein. The PSE-4 gene has limited homology with other beta-lactamases at the DNA level. An alignment of all known class A beta-lactamases permitted as to identify specific residues important for enzyme structure and function. To confirm observations based on the linear sequences, we designed a new molecular model for PSE-4 beta-lactamase based on x-ray data from the Staphylococcus aureus PC1 beta-lactamase at 2.0-A resolution. The structural similarities between PSE-4 and class A beta-lactamases are more extensive than indicated by earlier biochemical studies. The combined structural and sequence information now available for a series of beta-lactamases identifies conserved residues in these molecules, giving insight of their divergence and ancestry. Analysis of the PSE-4 flanking DNA sequences revealed an integration site common to antibiotic resistance genes inserted into transposons of the Tn21 family with the target integration sequence AAGTT.
Boissinot
M
M
Département de Microbiologie, Faculté de Médecine, Université Laval, Ste-Foy, Québec, Canada.
Levesque
R C
RC
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D010405:Penicillinase / Q000235:genetics*; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D013211:Staphylococcus aureus / Q000201:enzymology*; D001618:beta-Lactamases / Q000235:genetics*
D010405:Penicillinase; D001618:beta-Lactamases